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1.  Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis 
Age  2011;34(4):949-968.
Klotho (KL) gene has been involved in severe alterations of physiological biochemical parameters leading to premature aging-like phenotypes and strikingly shortening lifespan. KL participates to the regulation of a number of intracellular biochemical pathways, including lipid profile and glucose metabolism. Aim of this study was to investigate the possible association between KL locus and biological parameters commonly accepted as indicators of the clinical status in hospitalized older patients. We genotyped the single-nucleotide polymorphisms (SNPs) rs9536314, rs1207568, and rs564481 at the KL locus in 594 hospitalized older patients (65–99 years), consecutively attending a geriatric ward, and tested the association of these KL variants with biological quantitative traits using analyses of covariance and genetic risk score models. Significant associations of rs9536314 with serum levels of hemoglobin, albumin, and high-density lipoprotein cholesterol (HDL-C) as well as significant associations of rs564481 with serum levels of hemoglobin, fasting insulin, and fasting glucose were observed. Gender-segregated analyses confirmed these associations, and suggested that the associations of KL genotypes with HDL-C, fasting glucose and fasting insulin levels may be driven by the female gender, while the association with serum levels of hemoglobin may be driven by the male gender. The association of KL genotypes with creatinine levels was found only in females, while the association with insulin-like growth factor-1 (IGF-1) and lymphocytes count (LC) was found only in males. The genetic risk score (GRS) models further confirmed significant associations among KL SNPs and hemoglobin, total cholesterol, and HDL-C. Gender-segregated analyses with the GRS-tagged approach confirmed the associations with HDL-C, fasting glucose, and fasting insulin levels in females, and with hemoglobin and LC in males. Our findings suggested that KL locus may influence quantitative traits such as serum levels of lipid, fasting glucose, albumin and hemoglobin in hospitalized older patients, with some gender differences suggested for creatinine, IGF-1 levels, and LC, thus being one of the genetic factors possibly contributing to age-related diseases and longevity.
doi:10.1007/s11357-011-9273-x
PMCID: PMC3682056  PMID: 21695423
Klotho; Chromosome 13; High-density lipoprotein cholesterol; Total cholesterol; Fasting glucose; Fasting insulin; Insulin-like growth factor-1; Hemoglobin; Creatinine; Albumin; Lymphocytes
2.  Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients 
Age  2010;33(3):409-419.
The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR = 1.54, 95% CI 1.04–2.29). This association was significant in men (OR = 2.01, 95% CI 1.07–3.78), but not in women (OR = 1.36, 95% CI 0.82–2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.
doi:10.1007/s11357-010-9192-2
PMCID: PMC3168594  PMID: 21076879
Angiotensin-converting enzyme; Disability; Aging; Hospitalized patients
3.  Apolipoprotein E-related all-cause mortality in hospitalized elderly patients 
Age  2010;32(3):411-420.
The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 ± 7.1 years; range, 65–100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE ε2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37–0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the ε2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36–0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.
doi:10.1007/s11357-010-9144-x
PMCID: PMC2926860  PMID: 20640544
Apolipoprotein E; Mortality; Cardiovascular aging; Dementia
4.  Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene 
Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.
doi:10.4061/2011/721457
PMCID: PMC3090058  PMID: 21559196
5.  Association of Apolipoprotein E and Angiotensin Converting Enzyme Gene Polymorphisms with the Multidimensional Impairment in Older Patients 
Rejuvenation research  2009;12(4):239-247.
The role of the apoliprotein E (APOE) and the angiotensin converting enzyme (ACE) polymorphisms on health and functional status deterioration in old age is still undefined. Recently, a Multidimensional Prognostic Index (MPI) for 1-year mortality derived from a Comprehensive Geriatric Assessment (CGA) was developed and validated in hospitalized elderly patients. The aim of this study was to investigate the possible association of the APOE and ACE gene polymorphisms with the multidimensional impairment, as evaluated by the MPI, in older patients. These polymorphisms were assessed in 1894 geriatric inpatients divided into three groups according to their MPI values: MPI-1 low risk (n = 988), MPI-2 moderate risk (n = 671), and MPI-3 severe risk of mortality (n = 235). A slight deviation from Hardy–Weinberg equilibrium was observed for the APOE genotypes. With the increasing of the MPI grade, a significant increase in the frequencies of ε4 allele and the ACE D/D genotype was observed. The APOE ε4+ and ACE D/D genotypes were associated with severe MPI grade (APOE ε4+, odds ration [OR] = 1.79, 95% confidence interval [CI] 1.20–2.67; ACE D/D, OR = 1.42, 95% CI 1.05–1.92). The combined APOE ε4+ and ACE D/D genetic status was associated with higher MPI grade (OR = 2.85, 95% CI 1.75–4.65), without interaction. No significant associations between APOE and ACE polymorphisms and 2-year mortality were found. APOE and ACE genes might predispose individuals to health and functional status deterioration in old age, and their effect is additive.
doi:10.1089/rej.2009.0858
PMCID: PMC2868322  PMID: 19653879
6.  The Multidimensional Prognostic Index Predicts Short- and Long-Term Mortality in Hospitalized Geriatric Patients With Pneumonia 
Background
Multidimensional impairment of older patients may influence the clinical outcome of acute or chronic diseases. Our purpose is to evaluate the usefulness of a multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) for predicting mortality risk in older patients with community-acquired pneumonia (CAP).
Methods
This prospective study included 134 hospitalized patients aged 65 and older with a diagnosis of CAP. A standardized CGA that included information on clinical, cognitive, functional, and nutritional status as well as comorbidities, medications, and social support network was used to calculate MPI. The pneumonia severity index (PSI) was also calculated. The predictive value of the MPI for all cause mortality over a 1-year follow-up was evaluated and was compared with that of PSI.
Results
Higher MPI values were significantly associated with higher mortality at 30 days (Grade 1 = 3%, Grade 2 = 12%, Grade 3 = 44%, p < .001), 6 months (Grade 1 = 7%, Grade 2 = 21%, Grade 3 = 50%, p < .001), and 1 year (Grade 1 = 10%, Grade 2 = 33%, Grade 3 = 53%, p < .001). A close agreement was found between the estimated mortality by MPI and the observed mortality. MPI had a significant greater discriminatory power than PSI both at 30 days (area under the receiver operating characteristic [ROC] curve = 0.83 vs 0.71, p = .019) and 6 months (0.79 vs 0.69, p = .035), but not after 1 year of follow-up (0.80 vs 0.75, p = .185).
Conclusions
This MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients with CAP into groups at varying risk of short- and long-term mortality. The predictive accuracy of the MPI was higher than the predictive value of the PSI.
doi:10.1093/gerona/glp031
PMCID: PMC2981465  PMID: 19349589
Multidimensional prognostic index; Comprehensive geriatric assessment; Pneumonia; Mortality; Elderly people
7.  Association of Apolipoprotein E and Angiotensin Converting Enzyme Gene Polymorphisms with the Multidimensional Impairment in Older Patients 
Rejuvenation Research  2009;12(4):239-247.
Abstract
The role of the apoliprotein E (APOE) and the angiotensin converting enzyme (ACE) polymorphisms on health and functional status deterioration in old age is still undefined. Recently, a Multidimensional Prognostic Index (MPI) for 1-year mortality derived from a Comprehensive Geriatric Assessment (CGA) was developed and validated in hospitalized elderly patients. The aim of this study was to investigate the possible association of the APOE and ACE gene polymorphisms with the multidimensional impairment, as evaluated by the MPI, in older patients. These polymorphisms were assessed in 1894 geriatric inpatients divided into three groups according to their MPI values: MPI-1 low risk (n = 988), MPI-2 moderate risk (n = 671), and MPI-3 severe risk of mortality (n = 235). A slight deviation from Hardy–Weinberg equilibrium was observed for the APOE genotypes. With the increasing of the MPI grade, a significant increase in the frequencies of ɛ4 allele and the ACE D/D genotype was observed. The APOE ɛ4+ and ACE D/D genotypes were associated with severe MPI grade (APOE ɛ4+, odds ration [OR] = 1.79, 95% confidence interval [CI] 1.20–2.67; ACE D/D, OR = 1.42, 95% CI 1.05–1.92). The combined APOE ɛ4+ and ACE D/D genetic status was associated with higher MPI grade (OR = 2.85, 95% CI 1.75–4.65), without interaction. No significant associations between APOE and ACE polymorphisms and 2-year mortality were found. APOE and ACE genes might predispose individuals to health and functional status deterioration in old age, and their effect is additive.
doi:10.1089/rej.2009.0858
PMCID: PMC2868322  PMID: 19653879
8.  The Multidimensional Prognostic Index (MPI), Based on a Comprehensive Geriatric Assessment, Predicts Short- and Long-Term Mortality in Hospitalized Older Patients with Dementia 
Aim of this study was to evaluate the usefulness of a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) for predicting mortality risk in older patients with dementia. The present was a retrospective study with a year of follow-up that included 262 patients aged 65 years and older with a diagnosis of dementia. A standardized CGA that included information on clinical, cognitive, functional, and nutritional aspects, as well as comorbidity, medications, and social support network, was used to calculate MPI. The predictive value of the MPI for all-cause mortality over 1 month, 6 months, and 12 months of follow-up was evaluated. Higher MPI values were significantly associated with higher mortality at 1 month (MPI-1, low risk = 0%, MPI-2, moderate risk = 5.2%, MPI-3, severe risk = 13.7%; p < 0.002), 6-months (MPI-1 = 2.7%, MPI-2 = 11.2%, MPI-3 = 28.8%; p < 0.001), and 12-months (MPI-1 = 2.7%, MPI-2 = 18.2%, MPI-3 = 35.6%; p < 0.001) of follow-up. The discrimination of the MPI was also good, with areas under the ROC curves of 0.77 (sensitivity = 82.9%, specificity = 66.0%, with a cut off value > 0.16) at 12-months of follow up. In conclusion, the MPI, calculated from information collected in a standardized CGA, accurately stratified hospitalized elderly patients with dementia into groups at varying risk of short- and long-term mortality.
doi:10.3233/JAD-2009-1139
PMCID: PMC2864495  PMID: 19584441
Comprehensive Geriatric Assessment (CGA); dementia; mortality; Multidimensional Prognostic Index (MPI); prognosis; survival

Results 1-8 (8)